Potent, orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors

We combined the features of two structurally distinct series of SCD inhibitors that were previously reported by our group. This led to the discovery of compound CVT-12,012 which has single-digit nanomolar potency in a human HEPG2 SCD assay, 78% oral bioavailability in rats, and is preferentially distributed into liver. In a 5-day study (high sucrose diet, rat) CVT-12,012 significantly reduced liver triglycerides versus the control group (∼50%).